Population screening for haemochromatosis: expectations based on a study of relatives of symptomatic probands

The frequency of symptomatic haemochromatosis in the general population and the potential efficacy of population screening is uncertain. Data from family members of clinically diagnosed index cases were used to estimate the frequency of the haemochromatosis genotype, the proportion of homozygous individuals with clinical manifestations, and the efficacy of transferrin saturation and serum ferritin measurements as screening tests.

English language studies from Europe, North America, and Australia.

Haemochromatosis zygosity was classified only by HLA haplotyping, the most reliable available method. All subsequent analyses were based on family members classified in this way.

An estimated 53 individuals per 10,000 are homozygous for haemochromatosis. Overall, 67% of male and 41% of female family members display at least one clinical manifestation; for men, the frequency increases with age. Transferrin saturation levels are 70% or above in an estimated 72% of homozygous men, along with three per 1000 heterozygous or unaffected men. Transferrin saturation levels are 60% or above in an estimated 67% of homozygous women, along with six per 1000 heterozygous or unaffected women. Serum ferritin levels, but not transferrin saturation levels, are associated with clinical manifestations.

This information can be used to compare expected versus actual screening performance for intervention trials aimed at detecting haemochromatosis in the general population.